有丝分裂蛋白激酶及其上游调节信号在人肝癌组织中的表达

目的探讨有丝分裂原蛋白激酶(MAPK)通路在调控细胞的增殖和凋亡过程中所起到的作用.方法手术切除16份肝癌及癌旁组织标本,Western印迹检测ERK1、ERK2、JNK1、p38和MEK1、MEK2的蛋白含量.结果在本组的16例患者中,每例患者肝癌组织中的ERK1、ERK2、JNK1、p38蛋白表达显著高于癌旁组织,ERK1积分光密度值(Integral optic density IOD)在肝癌和癌旁组织中分别为300±98和98±48,差异有显著意义(P＜0.01).ERK2的IOD值在肝癌和癌旁组织中分别为587±83和232±96,差异有显著意义(P＜0.01);p38的IOD值在肝癌和癌旁组织中分别为270±85和107±88,差异有显著意义(P＜0.01);肝癌组织中的JNK1蛋白表达显著低于癌旁组织;JNK1的IOD值在肝癌和癌旁组织中分别为111±93和292±109,差异有显著意义(P＜0.01);MEK1、MEK2蛋白表达显著高于癌旁组织,MEK1的IOD值在肝癌和癌旁组织中分别为1418±244和806±90,差异有显著意义(P＜0.01),MEK2的IOD值在肝癌和癌旁组织中分别为1041±122和468±40,差异有显著意义(P＜0.05).结论在肝癌组织中细胞分裂增殖的信号传导通路ERK1、ERK2、MEK1、MEK2激酶处于高表达,JNK1激酶在肝癌组织中处于低表达,它们的失衡导致肝癌细胞生长失控和无限增殖的重要原因之一.JNK1和p38在肝癌组织中可能存在不同的激活途径.     

细胞外信号调节激酶及其上游激酶在人乳腺癌发生发展中的意义

目的　研究人乳腺癌组织、良性肿瘤以及瘤旁乳腺组织中细胞外信号调节激酶 (ERK1、ERK2 )及其上游激酶 (MEK1、MEK2 )的表达 ,以及术前化疗对MEK1、MEK2、ERK1、ERK2蛋白表达的影响。　方法　应用蛋白质印迹法检测 5 6例患者乳腺癌组织、8例乳腺良性肿瘤以及相应瘤旁组织中MEK1、MEK2及ERK1、ERK2蛋白的表达情况 ,其中 16例患者术前接受环磷酰胺 ,表阿霉素加 5 氟脲嘧啶或泰素加表阿霉素方案化疗。应用免疫组织化学方法检测乳腺癌组织及癌旁组织中MEK1、MEK2及ERK1、ERK2蛋白的表达。　结果　 4 0例未行术前化疗的乳腺癌组织中MEK2、ERK1、ERK2蛋白表达水平高于癌旁组织 ,分别为癌旁组织的 4 76、1 4 8和 2 0 9倍 (t值分别为 7 2 4 4 ,5 95 9,3 735 ,P <0 0 1) ;MEK1水平低于相应癌旁组织 (t=2 2 0 6 ,P <0 0 5 ) ;未行术前化疗的乳腺癌组织中MEK2、ERK1、ERK2蛋白表达水平高于乳腺良性肿瘤 (t值分别为 2 932 ,2 0 82 ,2 0 2 1,P <0 0 5 ) ;MEK1水平低于良性肿瘤 (t=2 0 75 ,P <0 0 5 ) ;雌激素受体阴性的乳腺癌中MEK2蛋白表达水平高于雌激素受体阳性的肿瘤 (t=2 4 0 ,P <0 0 5 ) ,MEK1蛋白表达水平低于雌激素受体阳性的肿瘤 (t =2 5 8,P <0 0 1) ;术前化疗的乳腺癌组织中MEK2蛋白表达     

人肝癌组织中核内转录基因Fos B和Jun D的表达及其意义

目的　探讨Fos和Jun的表达产物与人肝细胞癌发生、发展的关系。　方法　采用免疫组织化学S-P法和蛋白电泳技术对20例肝癌病人癌及癌旁组织中Fos和Jun核内癌蛋白的表达情况进行检测。结果　Westernblot结果示20例标本中有16例肝癌组织FosB、JunD蛋白含量高于癌旁组织。FosB光密度值在肝癌及癌旁组织中分别为2396±803和894±319,差异有显著意义（P＜0.01）;JunD光密度值在肝癌及癌旁组织中分别为1973±725和776±161,差异有显著意义（P＜0.05）。免疫组织化学结果显示FosB和JunD蛋白在肝癌组织细胞核中同步表达。　结论　在人原发性肝细胞癌组织中,核内转录基因FosB、JunD表达产物表达强度明显增高,这可能是肝细胞早期恶变的重要原因之一。     

EphrinA1在原发性肝细胞癌中的表达及临床意义

目的探讨原发性肝细胞癌中EphrinA1的mRNA和蛋白表达水平及其临床意义。方法应用逆转录聚合酶链反应（RT-PCR）及免疫组织化学方法检测EphrinA1的mRNA及蛋白在40例肝癌及相应的癌旁肝组织和10例正常肝组织中的表达水平,并分析其与临床病理学特点之间的关系。结果40例肝癌组织及相应的癌旁肝组织和10例正常肝组织中均有EphrinA1 mRNA的表达。RT-PCR分析显示EphrinA1mRNA在肝癌组织（0．5413±0．1527）中的表达显著高于癌旁肝组织（0．3895±0．0549,P〈0．05）和正常肝组织（0．3770±0．1055,P〈0．05）,而在癌旁肝组织（0．3895±0．0549）和正常肝组织（0．3770±0．1055）中的表达差异无统计学意义（P〉0．05）。从正常肝组织、癌旁肝组织到肝癌组织,EphrinA1蛋白的阳性表达率分别为20％（2／10）、35％（14／40）和62％（25／40）,呈递增趋势（x^2=14．762,P〈0．05）。EphrinA1蛋白的过表达与肝癌细胞的分化程度、门静脉癌栓的形成及淋巴结转移等临床病理因素有关（P〈0．05）。结论EphrinA1蛋白的过表达与肝癌细胞的分化程度、淋巴结转移和门静脉癌栓有密切联系,提示其可能在肝癌的恶性转化、侵袭和转移过程中发挥重要作用。     

细胞外信号调节激酶和P38蛋白激酶在自体移植静脉中的表达

目的研究丝裂原活化蛋白激酶亚单位细胞外信号调节激酶(ERK)和p38蛋白激酶(p38 MAPK)在移植静脉血管重塑过程中的表达.方法选Wistar大鼠80只,建立自体移植静脉模型,术后随机分为6 h、24 h、3 d、7 d、2周、4周、6周及8周组,于相应时点取材,半定量逆转录PCR法检测移植血管中ERK和p38 MAPK的mRNA表达;Western蛋白印迹定量检测ERK和p38 MAPK的蛋白产物及磷酸化蛋白产物表达;脱氧核苷酸末端转移酶末端标记法(TUNEL)检测血管平滑肌细胞(VSMC)凋亡的变化;免疫组化检测增殖细胞核抗原(PCNA)的表达.结果移植静脉术后6 h,ERK1和p38 MAPK的mRNA表达均明显增强,与正常静脉组比较差异均有显著性意义(P＜0.01);ERK1mRNA表达在移植后7 d达高峰,表达值为(33.2±14.2)%,p38 MAPK的mRNA表达于术后2周达到高峰,表达值为(58.8±26.2)%,与其余各时点比较差异有显著性意义(P＜0.01).Western蛋白印迹提示ERK1/2在术后1～2周达高峰,6周时逐渐恢复至正常水平;而p38 MAPK则在移植后2～4周达高峰,之后开始减少,8周时仍维持一定表达量(1/4～1/2).ERK1与PCNA表达呈正相关(r=0.759 6,P＜0.01),p38 MAPK与凋亡呈正相关(r=0.892 2,P＜0.01).结论MAPK的激活是移植静脉内膜增生以及血管重塑的关键环节,可能成为防治移植静脉狭窄、闭塞的新的治疗靶点.     

gax和HIF-1α基因在原发性肝癌组织中的表达及意义

目的探讨同源盒基因(gax)和缺氧诱导因子(HIF1α)表达产物与原发性肝癌发生、发展的关系。方法采用逆转录聚合酶链反应(RTPCR)和蛋白质印迹技术(Westernblot)分别检测20例原发性肝癌患者癌及癌旁肝组织中gax和HIF1α的mRNA以及蛋白质表达水平。结果肝癌组织中HIF1αmRNA(118.1±33.2)及蛋白表达(10.86±2.76)水平显著高于癌旁组织(分别为42.7±10.5与3.52±1.53,P均<0.05);肝癌组织中gaxmRNA表达(39.5±13.8)及其蛋白表达(4.10±1.26)水平低于癌旁组织(P均<0.05)。结论gax和HIF1α基因是调控肝癌组织血管生长的重要基因之一,与gax表达下调及HIF1α表达下调肝癌发生发展密切相关。     

p16/p38 MAPK/p53/Wip1通路在乳腺癌发生、发展中的作用及其临床意义

目的 探讨p16/p38 MAPK/p53/Wip1通路在乳腺癌发生、发展中的作用及其临床意义.方法 应用免疫组织化学方法检测70例乳腺癌组织、癌旁组织、20例正常乳腺组织中Wip1、p53、p38 MAPK、p16蛋白的表达,并对Wip1蛋白高表达与p53、p38、p16蛋白表达进行相关分析.结果 3种组织中Wip1蛋白高表达率分别为62.9%(44/70)、2.9%(2/70)、0(0/20).乳腺癌组织比癌旁组织、正常乳腺组织明显升高(P＜0.01).Wip1蛋白高表达与p53、p38、p16蛋白表达呈负相关(P＜0.01,等级相关系数rs分别为-0.529、-0.626、-0.499).结论 p16/p38 MAPK/p53/Wip1是负反馈通路,它可能在乳腺癌发生发展中起重要作用.     

CD95、JNK1、JNK2和c-Jun在肝细胞癌中的表达及意义

目的探讨CD95和JUK因子在肝细胞癌组织中的表达及生物学意义。方法采用免疫组化方法检测CD95、JNK1、JNK2和c-Jun蛋白在58例肝癌组织及其对应的癌旁肝组织中的表达水平。结合肝癌临床病理指标分析相关性。结果 CD95、JNK1、JNK2和c-Jun蛋白在癌旁肝组织中的阳性表达率为74.1%(43/58)、72.4%(42/58)、67.2%(39/58)、79.3%(46/58),高于在癌组织中的阳性表达率25.9%(15/58)、27.6%(16/58)、32.8%(19/58)20.7%(12/58),差异均具有统计学意义(P0.05);CD95蛋白的表达与JNK1(r=0.693,P=0.013)、JNK2(r=0.357,P=0.007)和c-Jun(r=0.670,P=0.021)蛋白的表达呈正相关。CD95、JNK1、JNK2和c-Jun蛋白表达水平和肝癌分化程度呈负相关(分别为r=-0.516,P=0.003;r=-0.364,P=0.006;r=-0.383,P=0.004;r=-0.508,P=0.003)。与性别、年龄、结节数目和有无肝硬化无关(P0.05)。结论 CD95蛋白肝癌组织中的表达下调,通过下游重要信号传导分子JNK1、JNK2和c-Jun的表达,导致肝癌细胞增殖和免疫逃逸是肝癌发生发展的重要分子机制。     

原发性肝细胞肝癌血小板源性生长因子的表达和肿瘤血管形成关系的相关研究

目的　初步探讨肝细胞性肝癌组织中血小板源性生长因子(platelet derived growthfactor,PDGF)及血管内皮细胞生长因子(vascular endothelial cell growth factor,VEGF)的表达与微血管密度(micro vessel density,MVD)的表达之间的关系。方法　对51 例肝癌组织及癌旁非肿瘤组织,20例正常肝组织,采用免疫组化(SABC法)检测PDGF、VEGF和CD34的表达。采用ELISA法,检测48例术前肝癌患者和16例肝内胆管结石患者血清中PDGF的浓度。结果　PDGF、VEGF在肝细胞癌组织中的阳性表达率分别为54.9%、64.7%,在癌旁非肿瘤组织中分别为 27.5%、37.3%,在正常肝组织中分别为5%、10%,三者之间比较差异有显著性意义(P<0.01),PDGF、VEGF阳性表达率与肝细胞癌的转移(P=0.031,P=0.04)、包膜形成(P=0.035, P=0.016)以及细胞分化程度(P=0.02,P=0.034)有关;与性别、年龄、肿瘤的大小没有关联。肝癌组织、癌旁组织和正常肝组织的MVD值分别是29.43±4.818、15.23±2.77(P<0.01)、14.56±1.96(P<0.01)。术前肝癌患者和肝内胆管结石患者血清中PDGF的浓度分别为458.33±303.17、125.00±92.69,二组之间比较有显著差异(P<0.05)。结论　PDGF在肝癌的发生,发展和浸润过程中可能起着重要促生长和转移作用,并且和VEGF可能存在一定的协同作用。     

凋亡抑制基因x-相关细胞凋亡抑制蛋白基因在肝癌细胞中的表达及临床意义

目的探讨x-相关细胞凋亡抑制蛋白基因（XIAP）mRNA及蛋白在肝癌组织和癌旁组织中的表达情况，及其与肝癌发生的关系。方法肝癌患者手术切除标本10例，应用半定量逆转录．聚合酶链反应（RT-PCR）分别检测肝癌组织和癌旁组织细胞XIAP mRNA基因的相对表达量，并通过免疫组织化学SP法检测10例肝癌组织和癌旁组织标本XIAP蛋白的表达情况。结果（1）半定量RT-PCR显示：XIAP基因在肝癌组织中均呈高表达，相对表达量为3．211±2．43，而在对应的癌旁组织中呈低表达或无表达，相对表达量为1．947±1．890，两组之间差异有统计学意义（P〈0．05）。（2）免疫组织化学及图像分析结果显示：在肝癌组织和癌旁组织中XIAP蛋白平均灰度扫描值分别为161．800±29．470和144．240±26．290，两组之间差异有统计学意义（P〈0．01）。结论XIAP在肝癌中的表达明显增高，可能在肝癌的发生、发展过程中发挥重要作用。     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.